Method to Create Multiple Primary Malignant Neoplasms with Stimulation of Tumor Growth under Conditions of Primary Immunodeficiency in Experiment.

The experimental model of synchronous multiple primary malignant tumors (MPMT) was created. B16/F10 melanoma (0.5 ml of suspension diluted 1:20 in saline) and sarcoma 45 (0.5 million tumor cells in 0.5 ml saline) were simultaneously subcutaneously inoculated to male BALB/c nude mice. In the model of synchronous MPMT, the tumors appeared faster by 2.4 times and had greater volumes: melanoma by 2.2 times and sarcoma by 3.2 times; melanoma metastasized into sarcoma in 71.4% cases; the survival of mice with MPMT was lower. The altered dynamics of malignant growth in the MPMT model is based on the mutual influence of tumors, which results in the exchange of "structural information".

Experimental Modeling of Multiple Primary Malignant Processes with One Tumor Suppressed by Another under Conditions of Primary Immunodeficiency.

The phenomenon of multiple primary malignant tumors (MPMT) is characterized by the presence of several primary neoplasms in the same patient. An experimental model of MPMT with one dominating tumor was developed. Female BALB/c nude mice received simultaneous subcutaneous inoculation of Guerin's carcinoma (5×105 tumor cells in 0.5 ml saline) and B16/F10 melanoma (0.5 ml suspension diluted 1:20 with saline). Control females received transplantation of either melanoma or carcinoma alone in the same doses and volumes. In animals with MPMT model, tumors appeared 3-fold faster than after isolated transplantation of melanoma or Guerin's carcinoma and were larger by 7.5 and 2.2 times, respectively; the survival of mice with MPMT was lower. Guerin's carcinoma in the MPMT model metastasized to melanoma and almost completely suppressed its growth. Thus, a MPMT model was created with carcinoma suppressing the malignant growth of melanoma.

Method for Stimulation of Malignant Growth by Chronic Pain in Rat Lungs.

We developed a method of reproducing malignant process in the lungs of rats with stimulation by chronic neurogenic pain. In white outbred male rats, chronic neurogenic pain was modeled by bilateral ligation of the sciatic nerves and in 45 days, a suspension of M1 sarcoma cells (106 cells/liter in 0.3 ml physiological saline) was injected into the subclavian vein. In almost all rats receiving transplantation of tumor cells against the background of chronic neurogenic pain, tumor foci in the lungs were detected in 1.5-2.0 months and led to the death of the animals.

[Influence of malignant growth and chronic neurogenic pain on neurosteroid levels in rat brain]. / Vliianie zlokachestvennogo rosta i khronicheskoi neirogennoi boli na uroven' neirosteroidov v mozge krys.

The aim of the study was to determine the level of sex steroid hormones in white matter of the brain of rats with tumors combined with chronic neurogenic pain (CNP), which was modeled by bilateral sciatic nerve ligation. The study included albino male rats (n=74). In the main group, M1 sarcoma was transplanted subcutaneously (n=11) or into the subclavian vein (n=11) 45 days after CNP modeling. Two comparison groups (n=13 each) included sham operated animals (without CNP) with M1 sarcoma transplanted subcutaneously and intravenously. Control groups included animals with CNP and sham operated animals. Rats were euthanized on day 21 of the carcinogenesis. Levels of total and free testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) in the brain white matter were measured using ELISA kits ("Cusabio", China). CNP caused a decrease in the total and free T by 1.5 times (p<0.05), E2 and P4 by 1.9 and 3 times, respectively, E3 by 1.6 times (p<0.05), as well as an increase in E1 by 1.4 times (p<0.05) as compared to the corresponding levels in the brain white matter of rats without CNP. CNP stimulated M1 sarcoma growth in both subcutaneous and intravenous transplantation. Regardless of the tumor site, the dynamics of total T, E2 and E3 in the brain had similar features, but the dynamics of free T, P4 and E1 differed. Thus, changes in the level of neurosteroids in the white matter of rat brain with CNP and tumor growth alone or associated with CNP are a reaction to stress.

Modeling of Lymphogenous and Hematogenous Metastasizing from Murine В16 Melanoma in Rats.

We developed a model of experimental melanoma. Intralienal xenogeneic transplantation of a suspension of melanoma cells B16 in physiological saline (0.1 ml; 1:10) was conducted to outbred male rats. In 6 months, histologically confirmed melanoma B16 in the spleen and its metastases in the liver, intestine, pancreas, adrenal glands, and lungs (hematogenous metastasis), as well as in the thymus and lymph nodes (lymphogenous metastasis) were revealed in rats. The proposed rat model of melanoma B16 metastasizes by the hematogenous and lymphogenous pathways, develops over 6 months, and allows receiving sufficient volume of material for analysis.

Sex-Related Characteristics of Systemic Hormonal Homeostasis in Rats with Sarcoma C-45 Cells Transplanted to the Lung.

Sex-related systemic status of pituitary and thyroid hormones and cortisol was studied in rats on days 7 and 14 after transplantation of sarcoma C-45 cells into the lung. Females demonstrated slower development of the tumor process (49.0±10.7 vs. 32.0±3.9 days in males). Injection of tumor cells causes similar disorders in the levels of ACTH, thyrotropic hormone, and prolactin in males and females and opposite disorders in the thyroid and glucocorticoid homeostasis associated in males (in contrast to females) with reduction of cortisol level (by 1.9 times) and increase in the concentrations of total thyroxine forms (by 1.4 times) and triiodothyronine (by 2.9 times) by day 14. Early sex-related shifts in the status of hormone that are a component of the adaptive system attest to their possible relationship with different course of the malignant process in male and female rats.

CHARACTERISTICS OF THYROID STATUS IN EXPERIMENTAL LIVER METASTASIS.

Aim of the study was to analyze the dynamics of thyroid hormones in the pituitary gland, thyroid gland (TG) and blood serum (BS) in liver metastases to reveal thyroid profile of metastasis and to find thyroid markers-of metastasis in BS. MATERIAL AND METHODS: The experiment included 44 white male rats weighing 180-250 g. Sarcoma 45 (S-45) was transplanted intrasplenically after the spleen was brought under the skin. Levels of thyroid hormones: thyroid stimulating hormone (TSH) in the pituitary gland, TG, BS; free (FT4) and total (T4) thyroxine and free (FT3) and total (T3) triiodothyronine in TG and BS were studied by radioimmunoassay (Immunotech, Czech Republic; Arian analyzer, Russia). RESULTS: From the first days of the tumor development, pituitary gland strain with TSH hyperproduction was observed, and later TG hypofunctioning developed. Quantitative changes of thyroid hormones in organs did not correspond to their dynamics in BS. First diagnostic signs of experimental liver metastases, under the absence of formed metastases in the organ, were hyper-TSH-emy and the tendency to FT3 decreasing in BS. Typical characteristics of the "climax" of liver metastasis included formation of a marked "low TB" syndrome which transformed into a more severe "lowT3/lowT4" syndrome in secondary metastasis to the lungs. CONCLUSIONS: Thus, primary tumor growth and development of metastases are accompanied by the strain and imbalanced functioning of the thyroid system. Analysis of dynamics of the thyroid axis hormones in BS allows prognosis of liver metastases, as well as contributes to identifying the point of no return for the disease development which leads to secondary metastasis and irreversible progression of the process.

A method for reproduction of metastases in the liver.

A new method for reproduction of metastatic involvement of the liver in outbred albino rats is proposed. The use of the method rules out the effects of stress factors (surgical intervention, total anesthesia) on malignant tumor metastasizing, making it maximally similar to the natural process. The method allows visual evaluation of the time course of the primary tumor node growth. The metastatic involvement of the liver develops only by the most significant route, hematogenic. The method can be used for the development of experimental therapy for this condition.

[Local level of neoangiogenesis factors in dynamics of experimental metastatic process in liver].

UNLABELLED: The aim--to study the dynamics content of VEGF-A, VEGF-R1, EGF and EGF-R1 in liver and spleen tissues from rats at different stages of liver metastases. MATERIALS AND METHODS: We have designed a model of liver metastases in male rats. The content of growth factors was examined by ELISA at 1, 2 and 5 weeks of carcinogenesis in tissue of liver and tumors of spleen. RESULTS: The content of growth factors increased in liver tissue at different stages of metastasis. The concentration of VEGF-A increased gradually from the 1st to 5th week carcinogenesis. The concentration of VEGF-R1 increased after 2 weeks and decreased slightly after 5 weeks of carcinogenesis. The level of all components of EGF/EGF-R1 increased after 2 weeks of carcinogenesis. CONCLUSION: The following pathogenetic aspects of liver metastasis were defined: change in levels of VEGF-A/VEGF-R1 indicating the progressive development of the process of neoangiogenesis, and increased levels of EGF/EGF-R1 responsible for metastasis processes.

[Dynamics of growth factors in the spleen and liver of rats at different stages of metastatic hepatic reconstitution].

UNLABELLED: The aim--to study the dynamics of IGF-I, IGS-II, TGF-ß1 in liver and spleen tissues from rats at different stages of liver metastases. MATERIALS AND METHODS: We have designed a model of liver metastases in male rats. The content of growth factors was examined by ELISA at 1, 2 and 5 weeks of carcinogenesis in tissue of liver and tumors of spleen. RESULTS: The content of growth factors increased in liver tissue at different stages of metastasis. The concentration of TGF-ß, increased from the first to the fifth week of carcinogenesis. The level of IGF-I increased after 2 weeks of carcinogenesis. CONCLUSION. Pathogenetic moments of metastasis to the liver are the change of growth factors levels, indicating intensification of metastasis from 2 weeks of carcinogenesis and proliferation from 1 to 5 weeks.

Effects of the standard and endoliquor injection of estradurin on the rat prostate.

The effects of intramuscular and endoliquor routes of administration of water-soluble antiandrogenic drug estradurin on proliferative activity of the prostate were studied. Estradurin injection via both routes produced a suppressive effect on the prostate. The effect of the minimum estradurin dose injected into the liquor was most manifest and not paralleled by side effects.